Parenteral solutions, such as the medical solutions administered in intravenous therapy for example, must be sterile when administered to the patient, and therefore must be sterile when packaged and stored. These sterile solutions were originally packaged in glass bottles and more recently in flexible containers such as plastic film bags. Flexible containers are preferred over glass containers due to advantages such as weight, ease of handling, disposability, and other considerations.
Conventionally the flexible container is fabricated and the solution is sealed in the container. Then the container and solution is terminally sterilized. The flexible container may be further packaged, shipped and then stored until needed.
The flexible container is manufactured of a plastic film or other material that is suitably compatible with the medical solution so as to minimize reaction with the solution or allow degradation and/or loss of potency during manufacture and/or storage. Suitable plastic material includes heat sealable PVC film for example.
A terminal sterilization method is selected so that the process is compatible with both the material of the flexible container and the medical solution therein. Suitable terminal sterilization methods include radiation sterilization and steam autoclaving, for example.
However, an increasing number of parenteral administered solutions, such as the new, biotechnically produced drugs, are not necessarily compatible with any combination of the presently known flexible containers and terminal sterilization processes currently in use. For example, some therapeutic solutions packaged in flexible containers lose their potency or change their composition if they are subjected to terminal sterilization by the traditional energy or chemical sterilization procedures. Energy sterilization processes include application of heat such as by steam autoclaving, or irradiation with Gamma, X-ray, microwave, plasma, for example. Chemical sterilization may include sterilization by liquid or vapor hydrogen peroxide, ethylene oxide (ETO), phenol, ethanol, or sodium hypochlorite for example.
The United States Food and Drug Administration (FDA) is currently recommending that all medical and surgical products be sterilized to a microbial survival probability of 10.sup.-6, an assurance that there is less than one chance in one million that viable micro-organism, such as viruses, bacteria, and spores, are present in the sterilized product.
For a general discussion of sterilization and techniques therefor. see The United States Pharmacopeia XXII, ch. 1211, pp 1705 et seq., Atkinson et al., Biochemical Engineering and Biotechnology Handbook, Stockton Press, New York, N.Y. (1983), pp. 875-886, and Demain et al., Manual of Industrial Microbiology and Biotechnology, American Society for Microbiology, Washington, D.C. (1986), pp. 345-362.
Thus there is a need for an alternative sterilization process that can be economically, efficiently, and safely used on-line with current filling processes.
There is also a need for a sterilizing and filling process that avoids using expensive packaging materials, and costly manufacturing and/or sterilization processes for large or small volume sterile packaging of known and new drugs for parenteral administration that have unique and sensitive characteristics, such as for example some of the biotechnically produced solutions or drugs.